In a groundbreaking study, Stevens researchers have shown how colorectal cancer evolves from mature intestinal cells back to stem cells. These findings explain why colorectal cancer is so resistant to treatment and may help develop effective treatments for intestinal tumors.
Colorectal cancer is the second leading cause of cancer death in the United States. Even more worrying is that the incidence of colorectal cancer is rising rapidly in adults under 55. Research has linked a combination of factors, including a Western diet high in processed foods, fats and sugar, a sedentary lifestyle, obesity, and changes in the gut microbiome, all of which can contribute to cell mutations and the growth of malignant tumors.
Although recent studies have pointed to stem cells as an important key factor in colorectal cancer, it is not clear exactly what is happening at the cellular level in the intestine. Now, a new study by researchers at Stevens Institute of Technology, Oncogenic stemness through dedifferentiation promotes tumor-persistent adaptability of the intestinal epithelium. Published in cell death and diseaseshed further light on the complex cellular environment of the intestine.
For this study, researchers led by Ansu Perekat, assistant professor in the Department of Chemistry and Chemical Biology at the Stevens School of Engineering and Science, focused on so-called Lgr5-positive stem cells. “These stem cells are essential for the rapid regeneration of tissue in the intestinal lining,” Professor Perekat explains. His research focuses on understanding why cancer often recurs after treatment, with the aim of informing treatment strategies that target tumor recurrence. “They are rapidly dividing cells that produce progenitor cells to constantly replace the intestinal lining.”
The intestines have a unique tissue structure. Lgr5-positive stem cells and their growing progenitors remain in small pocket-like regions called crypts until they are ready to “go out” to take on their designated role. Meanwhile, villi (tiny finger-like projections that line the small intestine and help absorb nutrients from food) are made up of mature, specialized cells that exit the crypts. As new cells move upward from the crypts into the villi, they normally stop dividing and take on their final role as mature cells.
In this setting, colon tumors can develop in two ways, Perekatt explains. One way is “bottom up”, where normal stem cells deep in the intestines mutate and become cancerous. The second “top-down” method occurs when mature cells near the surface of the intestine reprogram themselves to become stem-like again and then transform into cancer cells.
Mature cells can reverse their course and become stem-like again, especially after injury or when normal stem cells are lost. A similar process may occur in colon tumors, where mature, already specialized cells can acquire so-called de novo stemness and regain stem cell-like behavior. ”
Ansu Perekat, Assistant Professor, Stevens School of Engineering
In the study, Perekat’s team induced mutations in stem cell samples in mouse models and observed how they developed. The researchers noticed that while the mutant stem cells eventually replaced normal, healthy stem cells, a subset of the mutant progenitor cells became cancerous. “We don’t know why they change, or why only some of them change,” Perekat says. “It’s very random and sporadic. But when it changes, tumors develop.”
Additionally, the researchers observed that tumors that developed from cells that had newly acquired stemness were equipped with better survival mechanisms. “They had the ability to protect themselves from oxidative stress,” Perekat said, referring to oxygen-containing molecules that are naturally present in living organisms as part of cellular metabolism and can damage cells.
Colorectal cancer is notoriously difficult to treat because it is highly resistant to treatment. This study helps explain why. “Our study suggests that intestinal cancer can arise not only from damaged stem cells, but also from cells that revert to stem cells,” Perekat said. “These may contribute to why colorectal cancer is so diverse and resistant to treatment.”
Perekat’s findings could help develop new treatments for bowel cancer. “If you only treat cells that have become cancerous, rather than targeting cells that have newly acquired stemness, the cancer is more likely to come back,” Perekat says. “Therefore, understanding the causes of this reversion to stemness is critical to developing new and effective treatments for colorectal cancer.”
sauce:
Stevens Institute of Technology
Reference magazines:
Zugeib, K. Others. (2026). Oncogenic stemness through dedifferentiation promotes tumor-persistent adaptability in the intestinal epithelium. cell death and disease. DOI: 10.1038/s41419-026-08669-2. https://www.nature.com/articles/s41419-026-08669-2
